Mouse Conjunctival Forniceal Gene Expression During Postnatal Development and Its Regulation by Kruppel-like Factor 4

Overview

Journal Invest Ophthalmol Vis Sci

Specialty Ophthalmology

Date 2011 Mar 15

PMID 21398290

Citations 19

Authors

Divya Gupta

Stephen A K Harvey

Naftali Kaminski

Shivalingappa K Swamynathan

Affiliations

Soon will be listed here.

Abstract

Purpose: To identify the changes in postnatal mouse conjunctival forniceal gene expression and their regulation by Klf4 during the eye-opening stage when the goblet cells first appear.

Methods: Laser microdissection (LMD) was used to collect conjunctival forniceal cells from postnatal (PN) day 9, PN14 and PN20 wild-type (WT), and PN14 Klf4-conditional null (Klf4CN) mice, in which goblet cells are absent, developing, present, and missing, respectively. Microarrays were used to compare gene expression among these groups. Expression of selected genes was validated by quantitative RT-PCR, and spatiotemporal expression was assessed by in situ hybridization.

Results: This study identified 668, 251, 1160, and 139 transcripts that were increased and 492, 377, 1419, and 57 transcripts that were decreased between PN9 and PN14, PN14 and PN20, PN9 and PN20, and PN14 WT and Klf4CN conjunctiva, respectively. Transcripts encoding transcription factors Spdef, FoxA1, and FoxA3 that regulate goblet cell development in other mucosal epithelia, and epithelium-specific Ets (ESE) transcription factor family members were increased during conjunctival development. Components of pathways related to the mesenchymal-epithelial transition, glycoprotein biosynthesis, mucosal immunity, signaling, and endocytic and neural regulation were increased during conjunctival development. Conjunctival Klf4 target genes differed significantly from the previously identified corneal Klf4 target genes, implying tissue-dependent regulatory targets for Klf4.

Conclusions: The changes in gene expression accompanying mouse conjunctival development were identified, and the role of Klf4 in this process was determined. This study provides new probes for examining conjunctival development and function and reveals that the gene regulatory network necessary for goblet cell development is conserved across different mucosal epithelia.

Citing Articles

Molecular nature of ocular surface barrier function, diseases that affect it, and its relevance for ocular drug delivery.

Kaur S, Sohnen P, Swamynathan S, Du Y, Espana E, Swamynathan S Ocul Surf. 2023; 30:3-13.

PMID: 37543173 PMC: 10837323. DOI: 10.1016/j.jtos.2023.08.001.

Corneal epithelial development and homeostasis.

Swamynathan S, Swamynathan S Differentiation. 2023; 132:4-14.

PMID: 36870804 PMC: 10363238. DOI: 10.1016/j.diff.2023.02.002.

Dupilumab-Associated Mucin Deficiency (DAMD).

Barnett B, Afshari N Transl Vis Sci Technol. 2020; 9(3):29.

PMID: 32742759 PMC: 7354879. DOI: 10.1167/tvst.9.3.29.

Conjunctival goblet cells: Ocular surface functions, disorders that affect them, and the potential for their regeneration.

Swamynathan S, Wells A Ocul Surf. 2019; 18(1):19-26.

PMID: 31734511 PMC: 7004882. DOI: 10.1016/j.jtos.2019.11.005.

Membrane-associated mucins of the ocular surface: New genes, new protein functions and new biological roles in human and mouse.

Fini M, Jeong S, Gong H, Martinez-Carrasco R, Laver N, Hijikata M Prog Retin Eye Res. 2019; 75:100777.

PMID: 31493487 PMC: 10276350. DOI: 10.1016/j.preteyeres.2019.100777.

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